The Diabetes Prevention Trial of Type 1 Diabetes has been designed to test whether intervention during the prodromal period of the disease can delay its clinical onset. It is possible to identify impending clinical Type 1 DM through the detection of autoantibodies directed against self-antigens of the pancreatic B-cells. Since first degree relatives of probands with Type 1 DM have more than ten-fold the risk of Type 1 DM in the general population, the DPT-1 will focus on such relatives. Their initial blood (serum) screening will be for islet cell autoantibodies (ICA) detectable by the indirect immunofluorescence of cytoplasmic islet cell antigens in sections of normal human pancreas. Those individuals found to have ICA will then be staged into one of four different categories of risk of Type 1 DM, dependant upon their point of progression to the clinical disease. Type 1 DM risk assessment in non-diabetic relatives is based on a number of factors, including: genetic susceptability, age, the presence of ICA especially if found together with insulin response (FPIR) during an intravenous glucose tolerance test (IVGTT). In the DPT-1, "High Risk" relatives will be those that have been predicted to have at least a 50% probability of developing Type 1 DM within the next five years on the basis of positive ICA and low FPIR to IVGTT. Moderate risk relatives are those with positive ICA, but normal FPIR to IGTT. This group is further divisible into those with an "Intermediate Risk" on account of positive IAA and those with only a "Modest Risk" who are IAA negative. The "Low Risk" relatives lack ICA. The purpose of dividing subjects into these four predictive risk groups is that different intervention strategies are best applied to them because of their stage of natural history, while the invasiveness of the therapeutic approaches to be tested needs to be appropriately reconciled with the estimated risk of Type 1 DM in the different risk groups.